Pathogenic Mechanisms For Microvascular Disease The Formation of Advanced Glycosylated End Products AGEs

The effects of glucose in causing damage to the vascular cells can occur through the metabolism of glucose or through chemical changes that do not involve any enzyme activation. A high glucose concentration can lead to glycosylation of amino groups in proteins. The ultimate effect is the formation of advanced glycosylation end products (AGE). These AGEs can also form in other diseases like renal failure and normal aging. In diabetes mellitus the production and deposition of these products are thought to contribute to the development of the long-term microvascular complications. The AGE formation occurs especially with long half-life proteins like basement membrane. The AGEs bind to receptors and cause changes in signal transduction in macrophages or vascular endothelial cells. This in turn can lead to the release of various cytokines such as tumor necrosis factor, as well as oxidants. Recently AGEs and oxidants have been implicated in the increased expression of vascular endothelial growth factor (VEGF), which can increase vascular permeability and cause retinal angiogenesis (6,7).